Laboratoire de Glycochimie, des Antimicrobiens
et des Agroressources UMR 7378 CNRS


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Actualités et Publications

Insight on the Contribution of Plasmons to Gold-Catalyzed Solar-Driven Selective Oxidation of Glucose under Oxygen,

Golonu, S.; Pourceau, G.; Quéhon, L.; Wadouachi, A.; Sauvage, F.

Solar RRL 2020, 4, 2000084.

With the increasing concerns about pollution and reduction of energy demands, the use of solar energy to drive chemical transformations is becoming increasingly attractive. Within the context of sustainability, sunlight-driven organic transformation of biomass feedstock, such as free carbohydrates, to obtain high added-value products is an important topic in which the recent progress should contribute to the development of solar biorefineries. Among the variety of photocatalysts, gold nanoparticles (NPs) loaded onto large bandgap semiconductors represent the state of the art. Such catalysts are known to accelerate the targeted reaction upon plasmonic excitation. In addition, as noble metal NPs, they also hold an additional role related to surface catalysis, which has been exploited for aerobic oxidation of free sugars. Nevertheless, the respective contribution of each role during transformation is not well established. Herein, the enhancement of the O2-mediated oxidation of free sugars using Au NPs on CeO2 under standard air mass 1.5G illumination conditions is reported. The results highlight that the plasmonic contribution of Au NPs is totally annihilated and this enhancement stems solely from a thermal activation process induced by NIR radiation from standard white-light conditions.

First step to the improvement of the blood brain barrier passage of atazanavir encapsulated in sustainable bioorganic vesicles,

Nolay, F.; Sevin, E.; Létévé, M.; Bil, A.; Gosselet, F.; El Kirat, K.; Djedaini-Pilard, F.; Morandat, S.; Fenart, L.; Przybylski, C.; Bonnet, V.

Int. J. Pharm. 2020, 587, 119604.

The blood - brain barrier (BBB) prevents the majority of therapeutic drugs from reaching the brain following intravenous or oral administration. In this context, polymer nanoparticles are a promising alternative to bypass the BBB and carry drugs to brain cells. Amphiphilic cyclodextrins can form self-assemblies whose nanoparticles have a 100-nm-diameter range and are thus able to encapsulate drugs for controlled release. Our goal is to propose an optimized chemical synthesis of amphiphilic cyclodextrin, which remains a challenging task which commonly leads to only a low-milligram level of the high purity compound. Such cyclodextrin derivatives were used to prepare vesicles and to study their ability to vectorize a drug through the BBB. As a result, we introduced a convergent synthesis for a family of lipophosphoramidyl permethylated β-CDs (Lip-β-CDs) with various chain lengths. It was demonstrated that mixed vesicles comprised of phosphatidylcholine (POPC) and LipCDs were able to encapsulate atazanavir (ATV), a well-known protease inhibitor used as an antiretroviral drug against HIV. We highlighted that neo-vesicles promote the penetration of ATV in endothelial cells of the BBB, presumably due to the low fusogenicity of Lip-β-CDs.

Synthesis of defined oligohyaluronates-decorated liposomes and interaction with lung cancer cells,

Cano, M. E.; Lesur, D.; Bincoletto, V.; Gazzano, E.; Stella, B.; Riganti, C.; Arpicco, S.; Kovensky, J.

Carbohydr. Polym. 2020, 248, 116798.

In this work hyaluronic acid (HA) oligosaccharides with degree of polymerization (DP) 4, 6 and 8, obtained by enzymatic depolymerization of HA, were conjugated to a PEG-phospholipid moiety. The products (HA-DP4, HA-DP6 and HA-DP8) were used to prepare decorated liposomes. The cellular uptake of HA-DP4, HA-DP6 and HA-DP8-decorated fluorescently labelled liposomes was significantly higher (12 to 14-fold) in lung cancer cell lines with high CD44 expression than in those with low CD44 expression, suggesting a receptor-mediated entry of HA-conjugated formulations. Competition assays showed that the uptake followed this rank order: HA-DP8>HA-DP6>HA-DP4 liposomes. Moreover, they are capable of a faster interaction with CD44, followed by phagocytosis, than HA liposomes obtained from HA of higher molecular weight (4800 and 14800 Da). HA-DP4, HA-DP6 and HA-DP8-liposomes did not show cytotoxicity or inflammatory effects. Overall, we propose our new HA-DP oligosaccharides as biocompatible and effective tools for a potential drug delivery to CD44-positive cells.

Development of C-type lectin-oriented surfaces for high avidity glycoconjugates: towards mimicking multivalent interactions on the cell surface,

Porkolab, V.; Pifferi, C.; Sutkeviciute, I.; Ordanini, S.; Taouai, M.; Thepaut, M.; Vivès, C.; Benazza, M.; Bernardi, A.; Renaudet, O.; Fieschi, F.

Org. Biomol. Chem. 2020.

Multivalent interactions between complex carbohydrates and oligomeric C-type lectins govern a wide range of immune responses. Up to date, standard SPR (surface plasmon resonance) competitive assays have largely been to evaluate binding properties from monosaccharide units (low affinity, mM) to multivalent elemental antagonists (moderate affinity, µM). Herein, we report typical case-studies of SPR competitive assays showing that they underestimate the potency of glycoclusters to inhibit the interaction between DC-SIGN and immobilized glycoconjugates. This paper describes the design and implementation of a SPR direct interaction over DC-SIGN oriented surfaces, extendable to other C-type lectin surfaces as such Langerin. This setup provides an overview of intrinsic avidity generation emanating simultaneously from multivalent glycoclusters and from DC-SIGN tetramers organized in nanoclusters at the cell membrane. To do so, covalent biospecific capture of DC-SIGN via StreptagII /StrepTactin interaction preserves tetrameric DC-SIGN, accessibility and topology of its active sites, that would have been dissociated using standard EDC-NHS procedure under acidic conditions. From the tested glycoclusters libraries, we demonstrated that the scaffold architecture, the valency and the glycomimetic-based ligand are crucial to reach nanomolar affinities for DC-SIGN. The glycocluster 3.D illustrates the tightest binding partner in this set for a DC-SIGN surface (KD= 18 nM). Moreover, the selectivity at monovalent scale of glycomimetic D can be easily analyzed at multivalent scale comparing its binding over different C-type lectin immobilized surfaces. This approach may give rise to novel insights into the multivalent binding mechanisms responsible for avidity and make a major contribution to the full characterization of the binding potency of promising specific and multivalent immodulators.

Amide Synthesis by Transamidation of Primary Carboxamides,

Kolympadi Marković, M.; Marković, D.; Laclef, S.


The amide functionality is one of the most important and widely used groups in nature and in medicinal and industrial chemistry. Because of its importance and as the actual synthetic methods suffer from major drawbacks, such as the use of a stoichiometric amount of an activating agent, epimerization and low atom economy, the development of new and efficient amide bond forming reactions is needed. A number of greener and more effective strategies have been studied and developed. The transamidation of primary amides is particularly attractive in terms of atom economy and as ammonia is the single byproduct. This review summarizes the advancements in metal-catalyzed and organocatalyzed transamidation methods. Lewis and Brønsted acid transamidation catalysts are reviewed as a separate group. The activation of primary amides by promoter, as well as catalyst- and promoter-free protocols, are also described. The proposed mechanisms and key intermediates of the depicted transamidation reactions are shown.

Cyclodextrin complexation studies as the first step for repurposing of chlorpromazine,

Wang, Z.; Landy, D.; Sizun, C.; Cézard, C.; Solgadi, A.; Przybylski, C.; de Chaisemartin, L.; Herfindal, L.; Barratt, G.; Legrand, F.-X.

Int. J. Pharm. 2020, 584, 119391.

The antipsychotic drug chlorpromazine (CPZ) has potential for the treatment of acute myeloid leukemia, if central nervous system side-effects resulting from its passage through the blood–brain barrier can be prevented. A robust drug delivery system for repurposed CPZ would be drug-in-cyclodextrin-in-liposome that would redirect the drug away from the brain while avoiding premature release in the circulation. As a first step, CPZ complexation with cyclodextrin (CD) has been studied. The stoichiometry, binding constant, enthalpy, and entropy of complex formation between CPZ and a panel of CDs was investigated by isothermal titration calorimetry (ITC). All the tested CDs were able to include CPZ, in the form of 1:1, 1:2 or a mixture of 1:1 and 1:2 complexes. In particular, a substituted γ-CD, sugammadex (the octasodium salt of octakis(6-deoxy-6-S-(2-carboxyethyl)-6-thio)cyclomaltooctaose), formed exclusively 1:2 complexes with an extremely high association constant of 6.37 × 109 M−2. Complexes were further characterized by heat capacity changes, one- and two-dimensional (ROESY) nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations. Finally, protection of CPZ against photodegradation by CDs was assessed. This was accelerated rather than reduced by complexation with CD. Altogether these results provide a molecular basis for the use of CD in delayed release formulations for CPZ.

New biobased-zwitterionic ionic liquids: efficiency and biocompatibility for the development of sustainable biorefinery processes,

Huet, G.; Araya-Farias, M.; Alayoubi, R.; Laclef, S.; Bouvier, B.; Gosselin, I.; Cézard, C.; Roulard, R.; Courty, M.; Hadad, C.; Husson, E.; Sarazin, C.; Nguyen Van Nhien, A.

Green Chem. 2020, 22, 2935-2946.

A new family of biobased-zwitterionic ionic liquids (ZILs) have been synthesized starting from the renewable resource l-histidine natural amino acid and varying the lengths of the alkyl chains. These ZIL derivatives were firstly studied for their biocompatibility with different microorganisms including bacteria, molds and yeast. The obtained MIC values indicated that all the microorganisms were 5 to 25 times more tolerant to ZIL derivatives than the robust 1-ethyl-3-methylimidazolium acetate [C2mim][OAc] used as a reference. Modeling studies also revealed that the presence of the cation and the anion on the same skeleton together with the length of the N-alkyl chain would govern the biocompatibility of these neoteric solvents. Among the different synthesized ZILs, the N,N′-diethyl derivative has been demonstrated to be a suitable eco-alternative to the classically used [C2mim][OAc] for efficient pretreatment of harwood sawdust leading to a significant improvement of enzymatic saccharification. In addition, with up to a 5% w/v concentration in the culture medium, ZILs did not induce deleterious effects on fermentative yeast growth nor ethanol production.

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